Major histocompatibility complex (MHC) molecules function in the immune response by presenting antigenic peptides to T cells. Over two-hundred distinct types of human MHC (HLA) molecules are known, each capable of presenting an array of peptides that fit structurally into their binding regions. Peptides that bind well to one HLA type may bind poorly or not at all to another. In order to develop epitope-based vaccines, peptides that bind crossreactively to a large number of HLA types need to be defined. The overall objective of this project is to identify or synthesize antigenic peptides that are capable of binding to a wide range of HLA molecules. This will be done by a) searching for crossreactive peptides among proteins of various pathogens, b) chemically-modifying the crossreactive peptides as required to optimize binding, and c) testing their ability to be recognized by T cells from humans of diverse HLA types. This research should define the binding requirements of peptides for various HLA molecules as well as provide practical information on the design of T cell epitopes for vaccines and clinical monitoring studies.